Composite bone constructs and methods

ABSTRACT

Embodiments of the present technology include a method of making a bone composite graft for administration to a patient. The method may include combining a human cadaveric bone material with a plurality of polymethyl methacrylate binder particles and spincasting the combined human cadaveric bone material and polymethyl methacrylate binder particles to produce the bone composite graft. The method may also include ablating the bone composite graft to increase the surface area of bone material exposed. The human cadaveric bone material may be immobilized in the plurality of polymethyl methacrylate binder particles. The human cadaveric bone material may be present in an amount that is 50 weight percent of the bone composite graft, or less. Additionally, the bone composite graft may have a yield strength that is at least 13,000 N/cm2 and no greater than 15,000 N/cm2.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of commonly assigned U.S. patentapplication Ser. No. 14/713,627 filed May 15, 2015, which claims thebenefit of priority to U.S. Provisional Patent Application No.61/994,674 filed May 16, 2014, the entire content of which isincorporated herein by reference for all purposes.

BACKGROUND

Embodiments of the present technology are directed in general to thefield of medical grafts, and in particular to bone graft compositions,and methods of their use and manufacture.

Medical grafting procedures often involve the implantation ofautogenous, allograft, or synthetic grafts into a patient to treat aparticular condition or disease. The use of musculoskeletal allografttissue in reconstructive orthopedic procedures and other medicalprocedures has markedly increased in recent years, and millions ofmusculoskeletal allografts have been safely transplanted. A commonallograft is bone. Typically, bone grafts are resorbed and replaced withthe patient's natural bone upon healing. Bone grafts can be used in avariety of indications, including neurosurgical and orthopedic spineprocedures for example. In some instances, bone grafts can be used tofuse joints or to repair broken bones.

Allograft and autogenous bone are both derived from humans; thedifference is that allograft is harvested from an individual (e.g.,donor) other than the one (e.g., patient) receiving the graft. Allograftis often taken from donated cadavers so that their bone can be used forliving people who are in need of the bone, for example, patients whosebones have degenerated from cancer. Such tissues represent a gift fromthe donor or the donor family to enhance the quality of life for otherpeople.

Hence, bone graft compositions and methods are presently available andprovide real benefits to patients in need thereof. Yet many advances maystill be made to provide improved bone graft systems and methods fortreating patients. The bone graft systems and treatment and manufacturemethods described herein provide further solutions and answers to theseoutstanding needs.

BRIEF SUMMARY

Often, in recovering bone and other tissue from a donor, bone particlesor dust is generated while cutting bone. These bone particles arenormally considered waste and are discarded, providing no benefit topatients and limiting the reach of the donor's gift. Embodiments of thepresent technology may provide a way to use these bone particles andmaximize the benefit and reach of a donor's gift. Additionally,embodiments of the present technology may provide a bone graft withdesirable characteristics. These bone grafts may have sufficientstrength to substitute or supplement natural bone, while possessingflexibility and other mechanical properties similar to natural bone. Thebone grafts may be machined or formed into shapes that can be moreeasily implanted into a patient. Embodiments may also provide theadvantage of forming a bone graft that is actually larger in size thanthe bone from which the bone particles come. Furthermore, embodimentsmay also provide for consistent properties across the graft, and theability to tailor properties of the bone graft by adjusting processingparameters.

In a first aspect, embodiments of the present technology include a graftfor administration at a treatment site of a patient. The graft mayinclude a human cadaveric bone material immobilized in a polymericbinder. The human cadaveric bone material may include demineralized boneparticles. The demineralized bone particles may have an average diameterless than 1.1 mm, less than 750 μm, less than 500 μm, or less than 250μm. The human cadaveric bone material may include non-demineralizedbone, cancellous bone, and/or cortical bone in embodiments. In someembodiments, bone from animals other than humans may be used, and thepatient may be an animal other than a human.

The polymeric binder may promote cohesion between bone material with orwithout forming a bond between the polymer and the bone material. Inembodiments, the polymeric binder may be polylactic acid, cyano acrylate(e.g., Super Glue®), diphenylmethane diisocyanate, polymethylmethacrylate (PMMA), silicones, polyurethanes, or epoxies. In someembodiments, the polymeric binder may be a surgical glue or a bonecement. The polymeric binder may dissolve or may not dissolve in a humanbody. The bone graft may exclude a cross-linking agent. Additionally,the bone graft may include a polymer that is not cross-linked with across-linking agent. The polymeric binder may exclude a cross-linkingagent.

In the graft, the demineralized bone particles may be present in anamount between about 10 weight percent and about 70 weight percent,between about 10 weight percent and about 20 weight percent, betweenabout 20 weight percent and about 30 weight percent, between about 30weight percent and about 40 weight percent, between about 40 weightpercent and about 50 weight percent, between about 50 weight percent andabout 60 weight percent, or between about 60 weight percent and about 70weight percent.

In some embodiments, the bone graft may have a compressive modulusgreater than 7.0 GPa, greater than 7.5 GPa, greater than 8.0 GPa, orgreater than 8.5 GPa. The yield strength of the bone graft may begreater than 10,000 N, greater than 11,000 N, greater than 12,000 N,greater than 13,000 N, greater than 14,000 N, or greater than 15,000 N.Such compressive modulus and yield strengths may be measured on a 1 cm³sample of the bone graft.

The graft may have a surface area, where the human cadaveric bonematerial may be at least 50%, at least 60%, at least 70%, at least 80%,or at least 90% of the surface area in embodiments. The bone materialmay be considered in the polymeric binder even though bone material isexposed at a surface. Bone material exposed at a surface may still beadjacent to the polymeric binder and may be immobilized by the formationof the polymeric binder next to the bone material.

Bone grafts may include fibers, including muscle fibers and other humanfibers.

In another aspect, embodiments of the present technology include amethod of making a bone composite. The method may include adding aliquid to a plurality of human cadaveric particles to form a wetmixture. The liquid may include a plurality of monomers. The method mayalso include compacting the wet mixture to form a compacted wet mixture.The method may further include polymerizing the plurality of monomers toform a solidified polymer. The method may also include immobilizing theplurality of human cadaveric bone particles in the solidified polymer toform the bone composite.

The solidified polymer may or may not bond with the bone particles. Insome embodiments, the liquid with a plurality of monomers may fill invoids and spaces between bone particles, and then the formation of asolid polymer around the particles may immobilize the bone particles.PMMA may be an example of a polymer that immobilizes the bone particlesin this manner. PMMA may entrap bone particles without chemical bondingbetween the PMMA and the bone particles. In other embodiments, polymersmay bond with bone particles at a molecular level. For example, cyanoacrylate may bond with bone particles.

The wet mixture may also include a plurality of polymer particles. Thepolymer particles may include a polymer formed by polymerizing monomersof the same molecular formula as the monomers in the plurality ofmonomers. For example, the monomer may be methyl methacrylate (MMA), andthe polymer particles may include polymethyl methacrylate (PMMA). Theplurality of monomers and the plurality of polymer particles mayconstitute two parts of a formula for bone cement. In some embodiments,the method may include mixing the plurality of polymeric particles withthe human cadaveric bone particles before adding the liquid.

The wet mixture may not include a plurality of polymer particles. Forexample, the wet mixture may not include any polymethyl methacrylateparticles. The weight ratio of the plurality of polymer particles to theplurality of monomers in the wet mixture may be less than 3:1. Forexample, the weight ratio may be less than 70:30, less than 60:40, lessthan 50:50, less than 40:60, less than 30:70, less than 20:80, or lessthan 10:90.

The liquid may be at a temperature less than 60° F., less than 50° F.,less than 40° F., or less than 30° F. according to embodiments. Thepolymer particles and/or the bone particles may be at a temperature lessthan 60° F., less than 50° F., less than 40° F., or less than 30° F.according to embodiments.

The method may also include polymerizing the plurality of monomerswithin 10 minutes, 7 minutes, 5 minutes, 4 minutes, or 3 minutes ofadding the liquid.

The method may also include ablating the bone composite afterimmobilizing. Ablating the bone composite may include sanding ormachining the bone composite. Ablating the bone composite may increasethe surface area of the exposed bone particles.

In a further aspect, embodiments of the present technology include amethod of making a bone composite. The method may include densifying aplurality of human cadaveric bone particles to form a densifiedplurality of human cadaveric bone particles. Densifying the plurality ofhuman cadaveric bone particles may include densifying a plurality ofpolymer particles. Densifying the plurality of polymer particles mayinclude centrifuging or applying negative pressure.

The method may also include adding a liquid to the compacted pluralityof human cadaveric bone particles. The liquid may include monomers. Theliquid may be added to the compacted plurality of human cadaveric boneparticles with as fast a flowrate as possible. Polymerization may beginsoon after monomers contact polymer particles.

The method may also include mixing a plurality of human cadaveric boneparticles with a plurality of polymer particles before densifying. Thepolymer particles may include a polymer formed by polymerizing monomersof the same molecular formula as the monomers in the liquid.

The method may further include exposing the densified plurality of humancadaveric bone particles to a negative pressure before adding theliquid. For example, the human cadaveric bone particles may be exposedto a vacuum. The negative pressure may be applied while adding theliquid to the plurality of human cadaveric bone particles.

The method may further include polymerizing the monomers to form asolidified polymer. The method may also include immobilizing theplurality of human cadaveric bone particles in the solidified polymer toform the bone composite.

In yet another aspect, embodiments of the present technology may includea method of treating a bone defect in a human patient. The method mayinclude applying a bone graft to a treatment site of the human patient.The bone graft may include human cadaveric bone particles and apolymeric binder. The bone graft may be any bone graft or bone compositedescribed herein.

The bone defect may be a fracture, a disease, an infection, a void, or agenetic abnormality. The treatment site may be in the foot. For example,the bone graft may supplement or replace a navicular bone. Bone graftsmay also supplement or replace spine (vertebrae), bones in the hand,bones in the foot, ribs, or facial bones.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a block flow diagram of a method of making a bone compositeaccording to embodiments.

FIG. 2 shows a block flow diagram of a method of making a bone compositeaccording to embodiments.

FIG. 3 shows a system 300 for making bone composites according toembodiments.

FIG. 4 is a graph of load versus displacement for a bone compositeaccording to embodiments.

FIG. 5 is a microscope image of a slice of a bone composite according toembodiments.

DETAILED DESCRIPTION

Embodiments of the present technology may bond together bone particleswith a polymeric binder to form a bone graft or composite forimplantation in a patient. Embodiments include grafts and methods ofmaking composites that would use otherwise discarded bone particles.Embodiments may involve grafts or composites with consistent propertiessimilar to natural bone. What is more, processing parameters andcomposition parameters may be adjusted to affect the properties of thegraft or composite.

Conventional technologies do not provide the advantages of embodimentsof the present technology. Simply mixing polymeric binder and boneparticles may not provide a bone graft with consistent and desirableproperties. For example, mixing a polymeric binder and bone particle mayproduce a mixture with properties similar to bread dough. This mixturemay have voids and air pockets within the mixture, and the mixture maynot harden to form a composite with sufficient mechanical integrity toreplace or supplement natural bone. Other conventional technologies mayinclude synthetic composites, which may not have the flexibility ofnatural bone and may disintegrate under stress that normal bone canwithstand. Furthermore, synthetic composites, without natural bonepresent on its surface, may not facilitate the growth of natural bone onthe composite and may not integrate in a patient's body as well asembodiments of the present technology.

Turning to the figures, FIG. 1 shows a block flow diagram of a method100 of making a bone composite according to embodiments. Method 100 mayinclude adding a liquid with a plurality of monomers to a plurality ofhuman cadaveric bone particles to form a wet mixture 102. Mixing theliquid and bone particles together may form a wet mixture that has asoft, doughy consistency. Method 100 may also include compacting the wetmixture to form a compacted wet mixture 104. Compacting the wet mixturemay include packing the wet mixture into a container, such as acentrifuge tube. Compacting the wet mixture may include spincasting orcentrifuging the wet mixture, which may compact the particles and/orincorporate monomers in the voids between the particles. Thecentrifugation forces used can reach 100,000×g.

Method 100 may further include polymerizing the plurality of monomers106 to form a solidified polymer. Also, method 100 may includeimmobilizing the plurality of human cadaveric bone particles 108 in thesolidified polymer to form the bone composite. Without the polymer toact as a binder, the human cadaveric bone particles may otherwise not beimmobilized or stick together. The binder may or may not physically orcovalently bond with the bone particles. The bone composite may be anygraft described herein. Additionally, the monomer, bone particle, andpolymer may be any monomer, bone particle, and polymer described herein.

Turning to FIG. 2, this figure shows a block flow diagram of a method200 of making a bone composite. Method 200 may include densifying aplurality of human cadaveric bone particles 202. Also, method 200 mayinclude adding a liquid comprising monomers to the plurality of humancadaveric bone particles 204. The method may further includepolymerizing the monomers 206 to form a solidified polymer.Additionally, method 200 may include immobilizing the plurality of humancadaveric bone particles 208 in the solidified polymer to form the bonecomposite. The bone composite may be any graft described herein.Additionally, the monomer, bone particle, and polymer may be anymonomer, bone particle, and polymer described herein.

Methods and bone grafts may exclude cross-linking polymers.Cross-linking polymers may often involve cross-linking agents.Cross-linking agents may not be desired in the final bone graft and maybe difficult to remove if used to cross link polymers.

Method 200 may differ from method 100 in the order the liquid is addedand the particles are densified or compacted. In method 200, the liquidmay be added after initially densifying the plurality of human cadavericbone particles, while in method 100, the liquid may be added beforecompacting the particles. Method 200 may also include furtherdensification after liquid is added. Method 200 may be controllable andrepeatable and may not form an intermediate mixture with too low adensity.

Bone grafts and methods of forming bone composites and may involvedifferent ratios of bone and binder. Different ratios may affect thestrength and appearance of the final product. Bone may be stronger thanbinder. A higher ratio of bone may result in a stronger composite, atleast initially. The ratio may eventually become too large, with notenough binder to bond the bone material together.

Likewise, different ratios of polymer to monomer may be used in methodsof making bone composites. The ratio of the polymer powder, such asPMMA, to liquid monomer, such as MMA, may range from 0:100 to 75:25. Theratio may affect the strength and synthetic content of the finalproduct. Without any polymer particles initially with the boneparticles, the liquid monomer may be able to more effectively eliminatespace in the bone particles. However, the lack of polymers in the boneparticles may reduce the amount of polymerization of the monomer. Thus,decreasing the ratio of polymer to monomer may then decrease the spacesor voids between bone particles but may also decrease the amount ofpolymerization. This trade off would affect the strength of the finalcomposite. Ratios may also impact setting time, hardening time, andtemperature during the process. The polymerization may be exothermic,and hence the degree of polymerization may affect the heat generated inthe process.

The setting and hardening times may be affected by the temperature ofthe materials and the ambient environment. The liquid monomer, the boneparticles, and/or the polymer particles may be cooled in order toincrease the setting and hardening times.

Turning to FIG. 3, system 300 may be used to make bone composites bymethod 200. System 300 may include a reservoir 302. Reservoir 302 may bea cylinder or part of a syringe. Reservoir 302 may hold a plurality ofparticles 304. Particles 304 may include bone particles and optionallypolymer particles. A translatable partition 306 may move along thereservoir and against particles 304, resulting in decreased voids orsmaller voids between particles 304. Translatable partition 306 may be aplunger of a syringe. Translatable partition 306 may compact or densifyparticles 304. Translatable partition 306 may define an aperture 308,with one end of aperture 308 open to particles 304. The other end ofaperture 308 may be open to a fluid source 310. In this manner, a fluidfrom fluid source 310 may be delivered to particles 304. Fluid source310 may include monomers and/or a solvent. Aperture 308 may also bedefined by plastic, metal, or other tubing. The end of reservoir 302opposite aperture 308 may include a channel 312. Channel 312 may bedefined by plastic, metal, or other tubing. Channel 312 may be attachedto a pump 314. Pump 314 may create a vacuum or negative pressure inreservoir 302, specifically in the area that contains particles 304.This negative pressure may densify particles 304 and/or draw fluid fromfluid source 310, through aperture 308, and into voids in particles 304.The size of channel 312 or a filter in reservoir 302 may preventparticles 304 from exiting reservoir 302 or channel 312 and into pump314.

System 300 and method 200 may be combined with a method similar tomethod 100. For example, system 300 may be included in a centrifuge.Centrifuging may densify particles 304. Densifying by centrifuging mayoccur before or during the addition of fluid to particles 304.

FIG. 4 shows a graph of load versus displacement for a bone compositeformed by mixing 40% ground bone matrix (GBM) with a polymethylmethacrylate binder. GBM is bone that has not been demineralized. Thebone composite was formed with a spincasting method, which includedcentrifuging bone particles, polymer particles, and liquid monomer. A 1cm³ cube is subjected to compression testing to obtain the yield force(N) versus displacement (mm).

Turning to FIG. 5, a picture 500 is shown of the surface of a 0.5 mmthick slice from a composite of 50 weight percent demineralized boneparticles and 50 weight percent PMMA binder. Example demineralized boneparticles are distinguishable as amorphous structures 502, 504, and 506.FIG. 5 shows over 55% of the surface area as demineralized boneparticles. The more surface area that is demineralized bone, the morelikely the bone composite may have superior results in the body of ahuman patient. Exposed bone material in a bone composite may allow forbone growth or may allow for increased compatibility in the body.

Bone Composites Via Spincasting (Spincast Human Bone Composites)

In some embodiments, the purpose of the development is to make acadaveric human bone based structural graft that incorporates using asynthetic binder using centrifugation to create a strong long lastingbone based graft.

The development takes human cadaveric bone particles of specific sizesand combines with a synthetic binder. The ratio of each of thecomponents is optimized to give the required strength of natural humanbone, while minimizing the concentration of binder. The mixed componentsare then subjected to centrifugation forces to compact the particleswith incorporation of the binder in the voids between the particles. Thecentrifugation forces used can reach 100,000×g.

To make human cadaveric bone particles into strong lasting implantablegrafts using centrifugation.

The mode of operation is a structural graft that can withstand forcesexerted by the human body. The content of the graft makes the graftmostly natural human bone which in theory can lead to betterincorporation of the foreign graft into the host.

Bone particles do not stick together without the aid of a medium. Tomake a composite of bone that can withstand high levels of pressure andstress, the medium has to be substantially strong.

One such medium is cyano acrylate (Super Glue®) which is currently usedas surgical glue in humans that the body dissolves over a time. In thismethod the medium is used at its lowest possible concentration to yieldthe strength similar to human bone.

Other similar embodiments may include applying vacuum or chemicallymodifying the tissue to make it bind together. The method of usingcentrifugation (spincasting) to make the structure makes the applicationdifferent.

Human cadaveric bone is harvested and then section cleaned of softtissue and bodily fluids. It is next ground into particles that are lessthan 1.1 mm. The particles are then cleaned and demineralized via aproprietary method. The ground bone is then vacuum dried. From here thebone is used as is (Demineralized Bone Matrix-DBM) or is further groundto less the 250 microns to make a powder (Demineralized BonePowder-DBP). The binder component is currently cyano acrylate (SuperGlue®) and could be replaced with a number of other biocompatiblesynthetic glues.

The components, DBP, DBM, and binder are weighted out and combined thenmixed and placed in a centrifuge tube. The tubes are then centrifuged athigh rpm to compress the particles and to extrude any excess fluid tothe top. The centrifugation is run long enough to allow for the glue toset and then allowed to cure completely. Next the contents areextracted. The solidified plug is then machined via CNC into its finalconfiguration.

There are other glues that can be used as a binder.

Currently initial prototypes of compressed structures have been madewith bone and cyano based glue and currently testing compressionstrength of different combinations. Prototypes have also been machinedto evaluate how the formulation behaves during shaping.

Polylactic Acid (PLA) Coated Bone Particles

In further embodiments, the purpose of development is to make a bonebased powder that is coated with PLA to give the particles a binder foradhesion.

The development takes bone particles of any size and coats the outersurface either partially or completely. With the addition of PLA to thesurface of the particle, it now has a glue/binder that can be heated tocause the PLA to melt and form a solid.

To make bone particles moldable into strong long lasting configurations.

The PLA coated particles can be molded into a shape and then the moldheated to melt the PLA and get a solid, slowly dissolved (months)structure that can support substantial forces and stress.

Bone particles do not stick together without the aid of a medium. Tomake a composite of bone that can withstand high levels of pressure andstress the medium has to be substantially strong. One such medium is PLA(polylactic acid) and it is used as a human implant material that thebody dissolves over a long period of time. In this method the PLA isdissolved and then combined with bone particles and subsequently treatedto cause the PLA to solidify out of solution onto the surface of thebone particles/powder.

The product is made by obtaining clean and sterile bone particles/powderand then dissolving amorphous PLA in glacial acetic acid and combiningthe bone and the PLA solution to a dough consistency and no excessfluid. The dough mixture is then mixed with sodium bicarbonate tohomogeneity. The mixture is then exposed to water for injection (WFI) tocause a twofold reaction, one, the acetic acid combines with the sodiumbicarbonate and forms CO₂ gas, water, and Na ions, thereforeneutralizing the acetic acid. Second, the introduction of water causesthe PLA to precipitate on the surface of the bone particles. The mixtureis allowed to convert the acetic acid to gas and water and then themixture is washed followed by lyophilization.

Structural Bone Graft Composites

In yet further embodiments, the purposed of the development is to make acadaveric human bone based structural graft that incorporates usinghuman cadaveric fibers, human cadaveric proteins, and a synthetic binderusing isostatic pressure to create a strong long lasting bone basedgraft.

The development takes human cadaveric bone particles of specific sizesand combines with human cadaveric collagen fibers and a syntheticbinder. The ratios of each of the components are optimized to give therequired strength of natural human bone, while minimizing theconcentration of binder. The mixed components are then subjected to aninitial compaction to reduce the volume and then subjected to isostaticpressures (up to 66,000 psi), followed by a curing at elevatedtemperature for a specified time and then cooled. After cooling thegraft can be shaped mechanically into its final configuration.

To make human cadaveric bone particles into strong long lastingconfigurations using isostatic pressing.

The mode of operation is as a structural graft that can withstand forcesexerted by the human body. The content of the graft makes the graftmostly natural human tissue which in theory can lead to betterincorporation of the foreign graft into the host.

Bone particles do not stick together without the aid of a medium. Tomake a composite of bone that can withstand high levels of pressure andstress the medium has to be substantially strong. One such medium is PLA(polylactic acid) which is currently used as a human implant materialthat the body dissolves over a long period of time. In this method themedium is used at its lowest possible concentration to yield thestrength similar to human bone.

Human cadaveric bone is harvested and then section cleaned of softtissue and bodily fluids. It is next, ground into particles that areless than 1.1 mm. The particles are the cleaned and demineralized via aproprietary method. The ground bone is then vacuum dried. From here thebone is used as is (Demineralized Bone Matrix-DBM) or is further groundto less than 250 microns to make a powder (Demineralized BonePowder-DBP). Fibers for this project were obtained from a variety ofsources by ultimately used muscle fibers because muscle is abundantduring a recovery of other tissues. The muscle is cut into ˜3-8 cm³cubes and homogenized with saline solution. The homogenized muscles isthen freeze dried. Once dry the muscle is pulverized and sieved over a 1mm sieve. The retained fibers are collected. The fibers >1 mm are thentreated with 3-6% hydrogen peroxide and washed with saline. Theremaining fibers are then vacuum dried. Once dried they are untangledand used as is. The binder component is currently polylactic acid andcould be replaced with a number of other biocompatible syntheticplastics or glues.

The four components, DBP, DBM, fibers, and binder are weighed out andcombined then mixed and placed in a cylindrical mold. A plunger isinserted and then pressed using a hydraulic press to 15,000 to 18,000psi for approximately 5 minutes, next the pressed plug is removed fromthe mold and placed in a foam mold and sealed. The sealed mold is theninserted into the isostatic press and subjected to up to 66,000 psi fora specific time. Once the time has elapsed the mold is pulled out theisostatic press and extracted from the mold. The pressed plug is thenplaced in a compression device and pressed and heated for a specificamount of time at a specific elevated temperature (>50° C.). After theheating the compression device is removed from the oven and cooled toroom temperature and the plug is extracted. The plug is then shaped intoa final configuration using a CNC system with specific tooling.

Currently initial prototypes of compressed structures have been madewith the four components and currently testing compression strength ofdifferent combination. Prototypes have also been machined to evaluatehow the formation behaves during shaping.

Embodiments of the present technology can be better understood by thefollowing examples.

EXAMPLE 1

To determine mechanical properties of bone composites, a 1 cm³ cube ismachined from a casted bone composite. The cube is compressed and theyield force is measured. With returning reference to FIG. 4, the resultsfor two different samples of a composite of 40 weight percent groundbone matrix are shown. The results for one sample are indicated by thesolid line, and the results for another sample are indicated by thedashed line. The composite was made from spincasting a mixture of PMMAparticles, bone particles, and MMA liquid monomer initially at 10° C.

The maximum yield strength can be determined from a local maximum pointwhere the yield force stops increasing with displacement resulting fromcompression. With both these samples, the yield strength reaches a localmaximum at around 2 mm of displacement. The compression modulus isdetermined by the slope of the curve in the linear portion of the graphbefore the local maximum. This example showed a repeatable andquantifiable method for measuring the mechanical properties of a bonecomposite.

EXAMPLE 2

The mechanical properties of several bone composites and other materialswere tested in a manner similar to what was used in Example 1. Samplesof demineralized bone material with a PMMA binder formed by spincastingwere tested, including bone composites with 20%, 30%, 40%, 50%, and 66%demineralized bone material (DBM) by weight. Additionally, polyetherether ketone (PEEK), a thermoplastic polymer sometimes used as a bonegraft or implant, is tested. Navicular bone, a bone in the foot that maybe a candidate for a bone graft or implant, was also tested forcomparison. The resulting compressive modulus (GPa) and yield strength(N) of these tests is shown in Table 1. In addition, the publishedresult of cortical bone by D. T. Reilly and A. H. Burstein, “The Elasticand Ultimate Properties of Compact Bone Tissue,” J. Biomech., 8:393-405,1975, was listed for comparison.

TABLE 1 Compressive Modulus and Yield Strength of Bone MaterialsMaterial Compressive Modulus (GPa) Yield Strength (N) 20% DBM 7.5 14,02030% DBM 7.8 15,090 40% DBM 8.2 14,655 50% DBM 8.0 13,430 66% DBM 7.210,787 PEEK 3.5 9,500 Navicular 4.1 11,586 Cortical bone 17.9 20,500

As shown in Table 1, the demineralized bone material composites range incompressive modulus and yield strength. The bone composites have ahigher compressive modulus and yield strength than PEEK. PEEK, whilesometimes used as a bone graft or implant, may lack the flexibility ofbone and may crush at certain pressures. The relatively lower propertiesin Table 1 provide quantified data behind the observations of PEEK.Navicular bone has a compressive modulus and yield strength greater thanPEEK, indicating a higher flexibility than PEEK, but lower than the DBMbone composites tested. Cortical bone has a higher compressive modulusand yield strength than any bone composite or bone material tested.

This example shows that the compressive modulus and yield strength of abone composite could be adjusted at least by varying the concentrationof the DBM. This example also shows that the DBM bone composites canhave similar mechanical properties to human bones and have superiormechanical properties compared to other materials used for boneimplants.

EXAMPLE 3

The amount of surface area of a bone composite that is bone wasanalyzed. DBM particles were dyed with Coomassie Blue stain. After theDBM particles were dried, they were mixed with PMMA powder, and a 50weight % DBM bone composite was made using a spincasting method. A 0.5mm thick slice of the bone composite was shaved off and analyzed with alight microscope at 10× magnification. The resulting picture is shown inpreviously described FIG. 5.

The DBM particles are distinguishable as amorphous structures with blueoutlines. Examples of DBM particles in FIG. 5 include particles 502,504, and 506. Particles sizes of DBM in FIG. 5 range from 100 μm to 800μm. FIG. 5 was analyzed for the amount of surface area taken by DBM. TheDBM surface area was calculated to be 55.4%, and the binder surface areawas calculated to be 44.6%.

This example shows that greater than 50% of the surface area of acomposite may be bone material. This percentage may allow enough bone atthe surface of the composite to integrate with native bone in the bodyof a patient.

In the preceding description, for the purposes of explanation, numerousdetails have been set forth in order to provide an understanding ofvarious embodiments of the present technology. It will be apparent toone skilled in the art, however, that certain embodiments may bepracticed without some of these details, or with additional details.

Having described several embodiments, it will be recognized by those ofskill in the art that various modifications, alternative constructions,and equivalents may be used without departing from the spirit of theinvention. Additionally, a number of well-known processes and elementshave not been described in order to avoid unnecessarily obscuring thepresent invention. Additionally, details of any specific embodiment maynot always be present in variations of that embodiment or may be addedto other embodiments.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimits of that range is also specifically disclosed. Each smaller rangebetween any stated value or intervening value in a stated range and anyother stated or intervening value in that stated range is encompassed.The upper and lower limits of these smaller ranges may independently beincluded or excluded in the range, and each range where either, neither,or both limits are included in the smaller ranges is also encompassedwithin the invention, subject to any specifically excluded limit in thestated range. Where the stated range includes one or both of the limits,ranges excluding either or both of those included limits are alsoincluded.

As used herein and in the appended claims, the singular forms “a”, “an”,and “the” include plural referents unless the context clearly dictatesotherwise. Thus, for example, reference to “a method” includes aplurality of such methods and reference to “the monomer” includesreference to one or more monomers and equivalents thereof known to thoseskilled in the art, and so forth. The invention has now been describedin detail for the purposes of clarity and understanding. However, itwill be appreciated that certain changes and modifications may bepractice within the scope of the appended claims.

What is claimed is:
 1. A method of making a bone composite graft foradministration to a patient, the method comprising: combining a humancadaveric bone material with a plurality of polymethyl methacrylatebinder particles; spincasting the combined human cadaveric bone materialand polymethyl methacrylate binder particles to produce the bonecomposite graft, and ablating the bone composite graft to increase thesurface area of bone material exposed, wherein the human cadaveric bonematerial is immobilized in the plurality of polymethyl methacrylatebinder particles, wherein the human cadaveric bone material is presentin an amount that is 50 weight percent of the bone composite graft, orless, and wherein the bone composite graft has a yield strength that isat least 13,000 N/cm2 and no greater than 15,000 N/cm2.
 2. The method ofclaim 1, wherein the human cadaveric bone material comprisesdemineralized bone particles.
 3. The method of claim 2, wherein thedemineralized bone particles have an average diameter less than 1.1 mm.4. The method of claim 2, wherein the demineralized bone particles havean average diameter less than 250 μm.
 5. The method of claim 1, whereinthe bone composite graft has a compressive modulus that is at least 7.5GPa and no greater than 8.2 GPa.
 6. The method of claim 1, wherein thebone composite graft has a surface area, and at least 50% of the surfacearea is the human cadaveric bone material.
 7. The method of claim 1,wherein the human cadaveric bone material is present in an amount withina range from 20 weight percent of the graft to 50 weight percent of thebone composite graft.
 8. The method of claim 1, wherein the humancadaveric bone material is present in an amount within a range from 20weight percent of the graft to 40 weight percent of the bone compositegraft.
 9. The method of claim 1, wherein the human cadaveric bonematerial is present in an amount that is 30 weight percent of the bonecomposite graft.
 10. The method of claim 1, wherein the human cadavericbone material comprises demineralized bone material.
 11. The method ofclaim 1, wherein the bone composite graft has a surface area, wherein apercentage of the surface area is the human cadaveric bone material,wherein the human cadaveric bone material is present in an amount thatis a weight percent of the bone composite graft, and wherein thepercentage of the surface area that is human cadaveric bone material isgreater than the weight percent.
 12. The method of claim 11, wherein thepercentage of the surface area that is human cadaveric bone is greaterthan 50 percent and no more than 56 percent, and the weight percent is50 weight percent.
 13. The method of claim 1, wherein the bone compositegraft has a surface area, wherein a percentage of the surface area isthe human cadaveric bone material, wherein the human cadaveric bonematerial is present in an amount that is a weight percent of the bonecomposite graft, wherein the percentage of the surface area that ishuman cadaveric bone is 55.4 percent and the weight percent is 50 weightpercent.
 14. The method of claim 1, wherein the bone composite graftconsists of the human cadaveric bone material and the polymethylmethacrylate, and wherein the human cadaveric bone material is presentin an amount that is 50 weight percent of the bone composite graft, orless.
 15. The method of claim 1, wherein the human cadaveric bonematerial and the plurality of polymethyl methacrylate binder particlesare densified following the spincasting step.
 16. The method of claim15, wherein the plurality of polymethyl methacrylate binder particlesare present as a densified powder following the spincasting step.
 17. Amethod of making a bone composite graft for administration to a patient,the method comprising: combining a human cadaveric bone material, anamount of muscle fibers, and a polymeric binder; and compressing thecombined human cadaveric bone material, muscle fibers, and polymethylmethacrylate binder particles to produce the bone composite graft,wherein the human cadaveric bone material and the amount of musclefibers are immobilized in the polymeric binder.
 18. The method of claim17, wherein the polymeric binder comprises polylactic acid.
 19. Themethod of claim 17, wherein the binder comprises a biocompatiblesynthetic plastic.
 20. The method of claim 17, wherein the bindercomprises a biocompatible synthetic glue.
 21. A method of making a bonecomposite graft for administration to a patient, the method comprising:combining a plurality of human cadaveric bone particles with a pluralityof polymethyl methacrylate binder particles; spincasting the combinedhuman cadaveric bone particles and polymethyl methacrylate binderparticles to produce the bone composite graft, and ablating the bonecomposite graft to increase the surface area of bone material exposed,wherein the plurality of human cadaveric bone particles are immobilizedin the plurality of polymethyl methacrylate binder particles.
 22. Themethod of claim 21, wherein the human cadaveric bone particles comprisedemineralized bone particles.
 23. The method of claim 22, wherein thedemineralized bone particles have an average diameter less than 1.1 mm.24. The method of claim 22, wherein the demineralized bone particleshave an average diameter less than 250 μm.
 25. The method of claim 21,wherein the bone composite graft has a compressive modulus that is atleast 7.5 GPa and no greater than 8.2 GPa.
 26. The method of claim 21,wherein the bone composite graft has a surface area, and at least 50% ofthe surface area is the human cadaveric bone particles.
 27. The methodof claim 21, wherein the human cadaveric bone particles are present inan amount that is 50 weight percent of the bone composite graft, orless.
 28. The method of claim 21, wherein the human cadaveric boneparticles are present in an amount within a range from 20 weight percentof the bone composite graft to 50 weight percent of the bone compositegraft.
 29. The method of claim 21, wherein the human cadaveric boneparticles are present in an amount within a range from 20 weight percentof the bone composite graft to 40 weight percent of the bone compositegraft.
 30. The method of claim 21, wherein the human cadaveric boneparticles are present in an amount that is 30 weight percent of the bonecomposite graft.
 31. The method of claim 21, wherein the bone compositegraft has a yield strength that is from 13,000 N/cm2 to 15,000 N/cm2.32. The method of claim 21, wherein the bone composite graft has asurface area, wherein a percentage of the surface area is the humancadaveric bone particles, wherein the human cadaveric bone particles arepresent in an amount that is a weight percent of the bone compositegraft, and wherein the percentage of the surface area that is humancadaveric bone particles is greater than the weight percent.
 33. Themethod of claim 32, wherein the percentage of the surface area that ishuman cadaveric bone is greater than 50 percent and no more than 56percent and the weight percent is 50 weight percent.
 34. The method ofclaim 21, wherein the bone composite graft has a surface area, wherein apercentage of the surface area is the human cadaveric bone material,wherein the human cadaveric bone particles are present in an amount thatis a weight percent of the bone composite graft, wherein the percentageof the surface area that is human cadaveric bone particles is 55.4percent and the weight percent is 50 weight percent.
 35. The method ofclaim 21, wherein the bone composite graft consists of the humancadaveric bone particles and the polymethyl methacrylate, and whereinthe human cadaveric bone particles are present in an amount that is 50weight percent of the bone composite graft, or less.
 36. The method ofclaim 21, wherein the plurality of human cadaveric bone particles andthe plurality of polymethyl methacrylate binder particles are densifiedfollowing the spincasting step.
 37. The method of claim 21, wherein theplurality of polymethyl methacrylate binder particles are present as adensified powder following the spincasting step.